Hsp90-binding immunophilin FKBP51 forms complexes with hTERT enhancing telomerase activity
FK506-binding proteins are members of the immunophilin family of proteins. Those immunophilins associated to the 90-kDa-heat-shock protein, Hsp90, have been proposed as potential modulators of signalling cascade factors chaperoned by Hsp90. FKBP51 and FKBP52 are the best characterized Hsp90-bound im...
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todo:paper_15747891_v10_n7_p1086_Lagadari2023-10-03T16:27:37Z Hsp90-binding immunophilin FKBP51 forms complexes with hTERT enhancing telomerase activity Lagadari, M. Zgajnar, N.R. Gallo, L.I. Galigniana, M.D. FKBP51 FKBP52 Hsp90 hTERT Immunophilin Telomerase fk 506 binding protein fk 506 binding protein 51 fk 506 binding protein 52 heat shock protein 90 peroxide proteasome radicicol reactive oxygen metabolite telomerase telomerase reverse transcriptase unclassified drug fk 506 binding protein heat shock protein 90 protein binding tacrolimus binding protein 5 telomerase algorithm Article cancer cell cell fractionation cell nucleus cell survival cellular distribution confocal microscopy controlled study cytoplasm enzyme activity fibroblast gene overexpression genetic background human human cell immunofluorescence immunoprecipitation interphase mitochondrion oxidative stress priority journal protein localization quantitative analysis Western blotting metabolism protein degradation tumor cell line Cell Line, Tumor Cell Nucleus Cell Survival HSP90 Heat-Shock Proteins Humans Mitochondria Oxidative Stress Proteasome Endopeptidase Complex Protein Binding Proteolysis Tacrolimus Binding Proteins Telomerase FK506-binding proteins are members of the immunophilin family of proteins. Those immunophilins associated to the 90-kDa-heat-shock protein, Hsp90, have been proposed as potential modulators of signalling cascade factors chaperoned by Hsp90. FKBP51 and FKBP52 are the best characterized Hsp90-bound immunophilins first described associated to steroid-receptors. The reverse transcriptase subunit of telomerase, hTERT, is also an Hsp90 client-protein and is highly expressed in cancer cells, where it is required to compensate the loss of telomeric DNA after each successive cell division. Because FKBP51 is also a highly expressed protein in cancer tissues, we analyzed its potential association with hTERT·Hsp90 complexes and its possible biological role. In this study it is demonstrated that both immunophilins, FKBP51 and FKBP52, co-immunoprecipitate with hTERT. The Hsp90 inhibitor radicicol disrupts the heterocomplex and favors the partial cytoplasmic relocalization of hTERT in similar manner as the overexpression of the TPR-domain peptide of the immunophilin. While confocal microscopy images show that FKBP51 is primarily localized in mitochondria and hTERT is totally nuclear, upon the onset of oxidative stress, FKBP51 (but not FKBP52) becomes mostly nuclear colocalizing with hTERT, and longer exposure times to peroxide favors hTERT export to mitochondria. Importantly, telomerase activity of hTERT is significantly enhanced by FKBP51. These observations support the emerging role assigned to FKBP51 as antiapoptotic factor in cancer development and progression, and describe for the first time the potential role of this immunophilin favoring the clonal expansion by enhancing telomerase activity. © 2016 Federation of European Biochemical Societies Fil:Lagadari, M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Gallo, L.I. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_15747891_v10_n7_p1086_Lagadari |
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Universidad de Buenos Aires |
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I-28 |
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R-134 |
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Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
FKBP51 FKBP52 Hsp90 hTERT Immunophilin Telomerase fk 506 binding protein fk 506 binding protein 51 fk 506 binding protein 52 heat shock protein 90 peroxide proteasome radicicol reactive oxygen metabolite telomerase telomerase reverse transcriptase unclassified drug fk 506 binding protein heat shock protein 90 protein binding tacrolimus binding protein 5 telomerase algorithm Article cancer cell cell fractionation cell nucleus cell survival cellular distribution confocal microscopy controlled study cytoplasm enzyme activity fibroblast gene overexpression genetic background human human cell immunofluorescence immunoprecipitation interphase mitochondrion oxidative stress priority journal protein localization quantitative analysis Western blotting metabolism protein degradation tumor cell line Cell Line, Tumor Cell Nucleus Cell Survival HSP90 Heat-Shock Proteins Humans Mitochondria Oxidative Stress Proteasome Endopeptidase Complex Protein Binding Proteolysis Tacrolimus Binding Proteins Telomerase |
| spellingShingle |
FKBP51 FKBP52 Hsp90 hTERT Immunophilin Telomerase fk 506 binding protein fk 506 binding protein 51 fk 506 binding protein 52 heat shock protein 90 peroxide proteasome radicicol reactive oxygen metabolite telomerase telomerase reverse transcriptase unclassified drug fk 506 binding protein heat shock protein 90 protein binding tacrolimus binding protein 5 telomerase algorithm Article cancer cell cell fractionation cell nucleus cell survival cellular distribution confocal microscopy controlled study cytoplasm enzyme activity fibroblast gene overexpression genetic background human human cell immunofluorescence immunoprecipitation interphase mitochondrion oxidative stress priority journal protein localization quantitative analysis Western blotting metabolism protein degradation tumor cell line Cell Line, Tumor Cell Nucleus Cell Survival HSP90 Heat-Shock Proteins Humans Mitochondria Oxidative Stress Proteasome Endopeptidase Complex Protein Binding Proteolysis Tacrolimus Binding Proteins Telomerase Lagadari, M. Zgajnar, N.R. Gallo, L.I. Galigniana, M.D. Hsp90-binding immunophilin FKBP51 forms complexes with hTERT enhancing telomerase activity |
| topic_facet |
FKBP51 FKBP52 Hsp90 hTERT Immunophilin Telomerase fk 506 binding protein fk 506 binding protein 51 fk 506 binding protein 52 heat shock protein 90 peroxide proteasome radicicol reactive oxygen metabolite telomerase telomerase reverse transcriptase unclassified drug fk 506 binding protein heat shock protein 90 protein binding tacrolimus binding protein 5 telomerase algorithm Article cancer cell cell fractionation cell nucleus cell survival cellular distribution confocal microscopy controlled study cytoplasm enzyme activity fibroblast gene overexpression genetic background human human cell immunofluorescence immunoprecipitation interphase mitochondrion oxidative stress priority journal protein localization quantitative analysis Western blotting metabolism protein degradation tumor cell line Cell Line, Tumor Cell Nucleus Cell Survival HSP90 Heat-Shock Proteins Humans Mitochondria Oxidative Stress Proteasome Endopeptidase Complex Protein Binding Proteolysis Tacrolimus Binding Proteins Telomerase |
| description |
FK506-binding proteins are members of the immunophilin family of proteins. Those immunophilins associated to the 90-kDa-heat-shock protein, Hsp90, have been proposed as potential modulators of signalling cascade factors chaperoned by Hsp90. FKBP51 and FKBP52 are the best characterized Hsp90-bound immunophilins first described associated to steroid-receptors. The reverse transcriptase subunit of telomerase, hTERT, is also an Hsp90 client-protein and is highly expressed in cancer cells, where it is required to compensate the loss of telomeric DNA after each successive cell division. Because FKBP51 is also a highly expressed protein in cancer tissues, we analyzed its potential association with hTERT·Hsp90 complexes and its possible biological role. In this study it is demonstrated that both immunophilins, FKBP51 and FKBP52, co-immunoprecipitate with hTERT. The Hsp90 inhibitor radicicol disrupts the heterocomplex and favors the partial cytoplasmic relocalization of hTERT in similar manner as the overexpression of the TPR-domain peptide of the immunophilin. While confocal microscopy images show that FKBP51 is primarily localized in mitochondria and hTERT is totally nuclear, upon the onset of oxidative stress, FKBP51 (but not FKBP52) becomes mostly nuclear colocalizing with hTERT, and longer exposure times to peroxide favors hTERT export to mitochondria. Importantly, telomerase activity of hTERT is significantly enhanced by FKBP51. These observations support the emerging role assigned to FKBP51 as antiapoptotic factor in cancer development and progression, and describe for the first time the potential role of this immunophilin favoring the clonal expansion by enhancing telomerase activity. © 2016 Federation of European Biochemical Societies |
| format |
JOUR |
| author |
Lagadari, M. Zgajnar, N.R. Gallo, L.I. Galigniana, M.D. |
| author_facet |
Lagadari, M. Zgajnar, N.R. Gallo, L.I. Galigniana, M.D. |
| author_sort |
Lagadari, M. |
| title |
Hsp90-binding immunophilin FKBP51 forms complexes with hTERT enhancing telomerase activity |
| title_short |
Hsp90-binding immunophilin FKBP51 forms complexes with hTERT enhancing telomerase activity |
| title_full |
Hsp90-binding immunophilin FKBP51 forms complexes with hTERT enhancing telomerase activity |
| title_fullStr |
Hsp90-binding immunophilin FKBP51 forms complexes with hTERT enhancing telomerase activity |
| title_full_unstemmed |
Hsp90-binding immunophilin FKBP51 forms complexes with hTERT enhancing telomerase activity |
| title_sort |
hsp90-binding immunophilin fkbp51 forms complexes with htert enhancing telomerase activity |
| url |
http://hdl.handle.net/20.500.12110/paper_15747891_v10_n7_p1086_Lagadari |
| work_keys_str_mv |
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1807322718782095360 |